The first sequential reaction promoted by manganese: Complete stereoselective synthesis of (E)-α,β-unsaturated esters from 2,2-dichloroesters and aldehydes

Article abstract of DOI:10.1021/jo070209w

(Chemical Equation Presented) α,β-Unsaturated esters were obtained with complete control of stereoselectivity utilizing a sequential reaction of dichloroesters with a variety of aldehydes, promoted by active manganese. This methodology is generally applicable, and the C-C double bond can be di- or trisubstituted. A mechanism based on a successive aldol-type reaction/β-elimination is proposed to explain these results.

Full text of DOI:10.1021/jo070209w

The First Sequential Reaction Promoted by Manganese: Complete
Stereoselective Synthesis of (E)-r,â-Unsaturated Esters from
2,2-Dichloroesters and Aldehydes
Jose´ M. Concello´n,* Humberto Rodr´ıguez-Solla, Pamela D´ıaz, and Ricardo Llavona
Departamento de Qu´ımica Orga´nica e Inorga´nica, Facultad de Qu´ımica, UniVersidad de OViedo,
Julia´n ClaVer´ıa 8, 33071 OViedo, Spain
jmcg@unioVi.es
ReceiVed February 1, 2007
R,â-Unsaturated esters were obtained with complete control of stereoselectivity utilizing a sequential
reaction of dichloroesters with a variety of aldehydes, promoted by active manganese. This methodology
is generally applicable, and the C-C double bond can be di- or trisubstituted. A mechanism based on a
successive aldol-type reaction/â-elimination is proposed to explain these results.
Introduction
by Wittig,5 Horner-Wadsworth-Emmons,6 Heck,7 and Peter-
son reactions8 or via Cope rearrangements.9 These compounds
have also been prepared from acetylenic derivatives,10 R-sulfanyl
ester derivatives,11 E1cB-type processes,12 or via olefin me-
tathesis.13 Despite their unquestionable positive merits, almost
all these methodologies demonstrate some lack of control in
In contrast to other metals such as Li, Mg, Sm, and Cr, Mn-
(0) has enjoyed little application in organic synthesis, due, in
part, to the formation of an oxide layer on its surface.1 To
overcome this limitation, several approaches have been devel-
oped to increase its reactivity, and recently a variety of synthetic
applications of Mn(0)2 involving the use of active manganese3
have been reported. Therefore, bearing in mind both the minimal
toxicity and cost, metallic-active manganese could become an
important metal in organometallic transformations in the future.
The development of new methods for the stereoselective
formation of carbon-carbon double bonds is one of the most
demanding areas of research in organic chemistry.4 The
synthesis of R,â-unsaturated esters has commonly been achieved
(4) The Chemistry of Alkenes; Patai, S., Ed.; Interscience: New York,
1968; Vol. 2.
(5) (a) Aggarwal, V. K.; Fulton, J. R.; Sheldon, C. G.; de Vicente, J. J.
Am. Chem. Soc. 2003, 125, 6034-6035. (b) Hon, Y.-S.; Lu, L.; Chang,
R.-C.; Lin, S.-W.; Sun, P.-P.; Lee, C.-F. Tetrahedron 2000, 56, 9269-
9279. (c) Soucy, F.; Grenier, L.; Behnke, M. L.; Destree, A. T.; McCormack,
T. A.; Adams, J.; Plamondon, L. J. Am. Chem. Soc. 1999, 121, 9967-
9976. (d) Nicolaou, K. C.; Ha¨rter, M. W.; Gunzner, J. L.; Nadin, A. Liebigs
Ann./Recl. 1997, 1283-1301. (e) Spinella, A.; Fortunati, T.; Soriente, A.
Synlett 1997, 93-94. (f) Patil, V. J.; Ma¨vers, U. Tetrahedron Lett. 1996,
37, 1281-1284.
(6) (a) Ferguson, M. L.; Senecal, T. D.; Groendyke, T. M.; Mapp, A. K.
J. Am. Chem. Soc. 2006, 128, 4576-4577. (b) List, B.; Doehring, A.;
Fonseca, M. T. H.; Job, A.; Torres, R. R. Tetrahedron 2006, 62, 476-482.
(c) Ando, K. J. Org. Chem. 1999, 64, 6815-6821. (d) Ando, K. J. Org.
Chem. 1997, 62, 1934-1939. (e) Ando, K. Tetrahedron Lett. 1995, 36,
4105-4108.
(7) (a) Karimi, B.; Enders, D. Org. Lett. 2006, 8, 1237-1240. (b) Li,
J.-H.; Wang, D.-P.; Xie, Y.-X. Tetrahedron Lett. 2005, 46, 4941-4944.
(c) Moreno-Man˜as, M.; Pe´rez, M.; Pleixants, R. Tetrahedron Lett. 1996,
37, 7449-7452. (d) Beller, M.; Riermeier, T. H. Tetrahedron Lett. 1996,
37, 635-638.
(8) (a) Guevel, A. C.; Hart, D. J. J. Org. Chem. 1996, 61, 465-472. (b)
Welch, J. T.; Herbert, R. W. J. Org. Chem. 1990, 55, 4782-4784. (c)
Chenera, B.; Chuang, C.; Hart, D. J.; Lai, C. J. Org. Chem. 1992, 57, 2018-
2029. (d) Palomo, C.; Aizpuru´a, J. M.; Garc´ıa, J. M.; Gamboa, I.; Cossio,
F. P.; Lecea, B.; Lo´pez, C. J. Org. Chem. 1990, 55, 2498-2503.
(9) (a) Tamooka, K.; Nagasawa, A.; Wei, S.; Nakai, T. Tetrahedron Lett.
1996, 37, 8895-8898. (b) Tamooka, K.; Nagasawa, A.; Wei, S.; Nakai, T.
Tetrahedron Lett. 1996, 37, 8899-8900.
(1) Takai, K.; Ueda, T.; Hayashi, T.; Moriwake, T. Tetrahedron Lett.
1996, 37, 7049-7052.
(2) To see some synthetic applications of manganese: (a) Kakiya, H.;
Nishimae, S.; Shinokubo, H.; Oshima, K. Tetrahedron 2001, 57, 8807-
8815. (b) Kim, S.-H.; Rieke, R. D. J. Org. Chem. 2000, 65, 2322-2330.
(c) Guijarro, A.; Go´mez, C.; Yus, M. Trends Org. Chem. 2000, 8, 65-91.
(d) Cahiez, G.; Mart´ın, A.; Delacroix, T. Tetrahedron Lett. 1999, 40, 6407-
6410. (e) Kim, S.-H.; Rieke, R. D. Synth. Commun. 1998, 28, 1065-1072.
(f) Kim, S.-H.; Rieke, R. D. J. Org. Chem. 1998, 63, 6766-6767.(g) Tang,
J.; Shinokubo, H.; Oshima, K. Synlett 1998, 1075-1076. (h) Rieke, R. D.;
Kim, S.-H. J. Org. Chem. 1998, 63, 5235-5239. (i) Kim, S.-H.; Rieke, R.
D. Tetrahedron Lett. 1997, 38, 993-996. (j) Suh, Y.; Rieke, R. D.
Tetrahedron Lett. 2004, 45, 1807-1809.
(3) For preparations of active manganese (Mn*), see: (a) Fu¨rstner, A.;
Brunner, H. Tetrahedron Lett. 1996, 37, 7009-7012. (b) Kim, S. -H.;
Hanson, M. V.; Rieke, R. D. Tetrahedron Lett. 1996, 37, 2197-2200. (c)
Tang, J.; Shinokubo, H.; Oshima, K. Tetrahedron 1999, 55, 1893-1904
and reference 2d therein.
10.1021/jo070209w CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/15/2007
4396
J. Org. Chem. 2007, 72, 4396-4400

Synthesis of (E)-R,â-Unsaturated Esters
SCHEME 1. Synthesis of Disubstituted (E)-r,â-Unsaturated
Esters 3 and 5
the stereochemical outcome of the carbon-carbon double bond
formation, particularly when the double bond is trisubstituted;
other methods are either tedious (multistep processes) or involve
expensive starting materials and therefore have limited ap-
plicability.
As an alternative to the procedures mentioned above our
group has recently reported the non-preactivated manganese
promoted preparation of R,â-unsaturated esters with total
E-stereoselectivity from 2-bromo-3-hydroxyesters.14 This was
the first highly stereoselective â-elimination reaction mediated
by manganese. Despite the reactions proceeding in high yields
and with total stereoselectivity, the laborious preparation of the
starting materials constituted an important drawback.15 Previ-
ously, our group and other laboratories have reported the Zn,
SmI2, or CrCl2 mediated synthesis of R,â-unsaturated esters with
high or complete E-stereoselectivity through a sequential process
involving dihaloacetates and various aldehydes.16
reaction promoted by active manganese and starting from the
readily available dichloroesters 2 or 4 and aldehydes 1.
Results and Discussion
The sequential reaction of ethyl bromoacetate with aldehydes
promoted by nonactivated manganese, under a range of reaction
conditions, afforded the corresponding 3-hydroxyesters instead
of the desired unsaturated esters. To overcome this problem,
active manganese was therefore prepared by treatment of a
mixture of MnCl2 (13 mmol) and LiCl (26 mmol) with a slurry
of lithium powder (26 mmol) at room temperature.2d The
resultant black slurry promoted the reaction of model substrate
n-octanal with both alkyl dibromoacetate or alkyl dichloroacetate
in a similar manner, the latter reaction however being complete
only when performed at reflux in THF. The cost of starting
materials nevertheless led us to select dichloroacetate to study
further the scope of the reaction.20 Thus, the treatment of a
solution of a selection of aldehydes 1 (1 equiv) and the
corresponding alkyl dichloroacetate 2a-c21 (1.2 equiv) in THF
with active manganese (5 equiv) at reflux for 3 h afforded the
corresponding (E)-R,â-unsaturated esters 3a-m, after hydroly-
sis, with total E-stereoselectivity and in high yields (Scheme 1,
Table 1).
The simplicity, speed, and the use of readily available and
cheap starting materials are some of the features required in an
ideal synthesis, which utilizes sequential reactions. Sequential
reactions can be considered such as those processes that form
multiple carbon-carbon or carbon-heteroatom bonds in a
sequence of events without isolation of any intermediate. To
17
date, only a privileged group of reagents such as SmI2 or
18
CrCl2 are suitable for selective sequential processes.19 How-
ever, the cost of SmI2 or CrCl2 is a drawback, and cheaper
reagents are desirable for stereoselective sequential reactions.
In this paper, we describe a novel and completely stereoselective
synthesis of (E)-R,â-unsaturated esters 3 or 5 by a sequential
(10) (a) Zeitler, K. Org. Lett. 2006, 8, 637-640. (b) Katrizky, A. R.;
Feng, D.; Lang, H. J. Org. Chem. 1997, 62, 715-720. (c) Perisamy, M.;
Radhakrishnan, U.; Rameshkumar, C.; Brunet, J. Tetrahedron Lett. 1997,
38, 1623-1626.
(11) (a) Trost, B. M.; Parquette, J. R. J. Org. Chem. 1993, 58, 1579-
1681.(b) Tanikaga, R.; Miyashita, K.; Ono, N.; Kaji, A. Synthesis 1982,
131-132. (c) Tanaka K.; Uneme, H.; Ono, N.; Kaji, A. Chem. Lett. 1979,
1039-1040.
(12) (a) Feuillet, F. J. P.; Cheeseman, M.; Mahon, M. F.; Bull, S. D.
Org. Biomol. Chem. 2005, 3, 2976-2989.(b) Feuillet, F. J. P.; Robinson,
D. E. J. E.; Bull, S. D. Chem. Commun. 2003, 2184-2185.
(13) (a) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int.
Ed. 2005, 44, 4490-4527. (b) Straus, D. A.; Grubbs, R. H. J. Mol. Catal.
1985, 28, 9-19. (c) Brown-Wensley, K. A.; Buchwald, S. L.; Cannizzo,
L.; Clawson, L.; Ho, S.; Meinhardt, D.; Stille, J. R.; Straus, D.; Grubbs, R.
H. Pure Appl. Chem. 1983, 55, 1733-1744.
(14) Concello´n, J. M.; Rodr´ıguez-Solla, H.; del Amo, V. Synlett 2006,
315-317.
(15) The reaction between an enolate derived from a 2-bromoester and
the carbonyl compound affords, in high yields, the corresponding 2,3-
epoxyester (Darzens’ reaction) as the major product instead of the desirable
2-bromo-3-hydroxyester, consequently the reaction must be carried out at
low temperatures (-90 °C).
The diastereoisomeric ratio of compounds 3 was determined
by GC-MS analysis and examination of the 1H NMR spectrum
(300 MHz) of the crude reaction products 3a-m. In all cases,
the E-stereoisomer was isolated as a single isomer and no
Z-isomer was detected in the crude products. The relative
configuration of the C-C double bonds in compounds 3 was
1
assigned on the basis of the magnitude of H NMR coupling
constant between the olefinic protons22 and/or by comparison
of their NMR spectra with those described in the literature for
the same unsaturated esters (see the experimental section).
In Table 1 the results obtained with active manganese are
compiled, and in a few cases, for comparison, yields with SmI2
or CrCl2 are also given. Several points are worth noting: (1)
(16) (a) Concello´n, J. M.; Concello´n, C.; Me´jica, C. J. Org. Chem. 2005,
70, 6111-6113. (b) Barma, D. K.; Kundu, A.; Bandyopadhyay, A.; Kundu,
A.; Sangras, B.; Briot, A.; Mioskowski, C.; Falck, J. R. Tetrahedron Lett.
2004, 45, 5917-5920. (c) Only one example (ethyl 3-phenylprop-2-enoate)
has been synthesised using a sequential reaction of ethyl dibromoacetate
and benzaldehyde promoted by Fe(0): Falk, J. R.; Bejot, D. K.; Bandyo-
padhyay, A.; Joseph, S.; Mioskowski, C. J. Org. Chem. 2006, 71, 8178-
8182. (d) Using a zinc-metal-promoted olefination: Ishino, Y.; Mihara, M.;
Nishihama, S.; Nishiguchi, I. Bull. Chem. Soc. Jpn. 1998, 71, 2669-2672.
(17) For recent reviews of SmI2-promoted sequential reactions, see: (a)
Molander, G. A.; Harris, C. R. Chem. ReV. 1996, 92, 307-338. (b)
Molander, G. A.; Harris, C. R. Tetrahedron 1998, 54, 3321-3354; For
recent reviews of synthetic applications of SmI2 see: (c) Krief, A.; Laval,
A. M. Chem. ReV. 1999, 99, 745-777. (d) Steel, P. G.; J. Chem. Soc.,
Perkin Trans. 1 2001, 2727-2751. (e) Kagan, H. B. Tetrahedron 2003,
59, 10351-10372. (f) Concello´n, J. M.; Rodr´ıguez-Solla, H. Chem. Soc.
ReV. 2004, 33, 599-609. (g) Dahle´n, A.; Hilmerson, G. Eur. J. Inorg. Chem.
2004, 3393-3403.
(18) For reviews of synthetic applications of CrCl2, see: (a) Takai, K.
Org. React. 2004, 64, 253-612. (b) Liu, Y.; Wu, H.; Zhang, Y. Synth.
Commun. 2001, 31, 47-52. (c) Matsubara, S.; Oshima, K. In Modern
Carbonyl Olefination; Takeda, T., Ed.; Wiley-VCH: Weinheim, Germany,
2004; Chapter 5. (d) Fu¨rstner, A. Chem. ReV. 1999, 99, 991-1045. (e)
Wessjohann, L. A.; Scheid, G. Synthesis 1999, 1-36. To see some examples
of CrCl2-promoted sequential reactions: (f) Barma, D. K.; Kundu, A.;
Bandyopadhyay, A.; Sangras, B.; Briot, A.; Mioskowski, C.; Falck, J. R.
Tetrahedron Lett. 2004, 45, 5917-5920. (g) Barma, D. K.; Kundu, A.;
Zhang, H.; Mioskowski, C.; Falck, J. R. J. Am. Chem. Soc. 2003, 125,
3218-3219.
(19) To see a recent Fe(0)-mediated sequential reaction (utilized in the
synthesis of ethyl 3-phenylprop-2-enoate), see ref 16c.
(20) Alfa Aesar catalogue (2007): Br2CHCO2Et (5 g, 28.60 euro);
Aldrich catalogue (2007-2008): Cl2CHCO2Me (5 g, 0.14 euro); Cl2-
CHCOCl (5 g, 8.70 euro). Cl2CHCO2t-Bu was easily obtained from Cl2-
CHCOCl.
(21) Compounds 2a and 2b were available from commercial sources.
J. Org. Chem, Vol. 72, No. 12, 2007 4397

Concello´n et al.
TABLE 1. Synthesis of Disubstituted r,â-unsaturated Esters 3
TABLE 2. Synthesis of Trisubstituted r,â-unsaturated Esters 5
yield (%)a
entry
5
R1
R3
yield (%)a
b
b
entry
3
R1
n-C7H15
Cy
i-Bu
R2
Et
Me
Et
Mn
SmI2
CrCl2
1
2
3
4
5
5a
5b
5c
5d
5e
n-C7H15
n-C7H15
Cy
i-Bu
i-Bu
Me
PhCH2
Me
Me
PhCH2
73
85
70
68
88
1
2
3
4
5
6
7
8
9
10
11
12
13
3a
3b
3c
3d
3e
3f
3g
3h
3i
83
87
89
92
85
89
78
88
90
81
72
92
88
66
60
d
75
84c
e
s-Bu
Et
d
e
69c
d
88c
e
a Yields of the isolated products after column chromatography; diaste-
reoisomeric ratio (dr) > 98% was determined from crude reaction products
with GC-MS and/or H NMR (300 MHz).
PhCH(Me)
PhCH2CH2
PhCH2CH2
CH2)CH(CH2)8
PhCHdCH
Ph
Me
Me
t-Bu
Et
Et
Et
Me
Et
Et
1
d
d
d
81
d
e
e
79
95
e
72
e
3j
3k
3l
propionate 4a or 3-phenyl-2,2-dichloropropionate 4b prepared
by alkylation of the lithium enolate of ethyl dichloroacetate with
the requisite alkyl halide (MeI or PhCH2Br) (Scheme 1, and
Table 2).
Total stereoselectivity was again observed and ascertained
as above. The relative configuration of compounds 5a-e was
assigned by NOESY experiments, with an nuclear Overhauser
effect being observed between PhCH2 and n-C6H13CH2 in
compound 5b and/or by comparison of their NMR spectra (5a
and 5c) with those previously described in the literature for the
same unsaturated esters.25 The E-stereochemistry of compounds
5d and 5e was assigned by analogy.
Literature data indicate that increasing substitution around
the double bond usually results in diminished stereoselectivity.
The manganese-based methodology differs from the others in
that no Z-isomer was detected in the crude samples. Analysis
of Table 2 reveals that the synthesis of trisubstituted unsaturated
esters is general, allowing for the use of linear, cyclic, or
branched aldehydes. However, when the sequential reaction was
carried out with ketones (acetophenone and 3-pentanone),
complex mixtures of unidentified products were obtained.
Mechanism. Formation of R,â-unsaturated esters 3 and 5
using active manganese can be explained by assuming a
sequential process (Scheme 2). Thus, reaction of 1 equiv of Mn*
with the corresponding dichloroester 2 or 4 generates a
manganese enolate 6, which reacts with the aldehyde 1 affording
the corresponding 2-chloroester 7. Metalation of 7 with an
additional equivalent of manganese affords the enolate inter-
mediate 8 which undergoes a further 1,2-elimination process.
The total stereoselectivity observed in the â-elimination
reaction can be explained by considering the probable chelation
of the MnII center by the oxygen atom of the alcohol group.
We propose a half-chair transition state model I in which the
bulkier group R1 is pseudo-equatorial. As depicted in the C2-
C3 Newman projection II, R1 and R3 have a cis relationship
leading to the E-stereoisomers 3 and 5 upon elimination. In
addition, thermodynamic control of the elimination would afford
the E-isomer.
Ph
p-MeOC6H4
p-ClC6H4
70
d
3m
a Isolated yields; diastereoisomeric ratio (dr) > 98% was determined from
crude reaction products with GC-MS and/or 1H NMR (300 MHz).
b Reference 16a. c This reaction was performed with the ethyl ester instead
of the methyl ester. d This process was not carried out by using SmI2 as
metalation agent. e This reaction was not carried out using CrCl2.
The active manganese used to promote this reaction is cheap,23
presents low toxicity, and is readily obtained. (2) The sequential
synthesis of R,â-unsaturated esters seems to be general. Thus,
aliphatic (linear, branched, or cyclic) and aromatic (E)-R,â-
unsaturated esters can be obtained, and in addition other alkyl
dichloroacetates such as methyl or t-butyl esters (2b, and 2c,
respectively) can be used. (3) The method is very efficient and
R,â-unsaturated esters are obtained in high yields. (4) In contrast
to other previously described syntheses of R,â-unsaturated acid
derivatives, this preparation can be carried out by using readily
enolizable aldehydes24 (Table 1, entry 5). (5) Other function-
alities are compatible with the transformation, such as ethers,
chlorine, and C-C double bonds (Table 1, entries 8, 9, 12, and
13). (6) Comparison between these results and those obtained
with SmI2 or CrCl2 (Table 1) reveals that the combination of
active manganese and dichloroacetate is at least competitive with
the use of the more expensive dibromoacetate20 and either
SmI2,16a CrCl2,16a,b or Fe(0).16c (7) This methodology also
compares favorably with the Wittig reaction in terms of yields
(e. g., esters 3c,5c 3f,5b 3g,5b and 3m5a) and with any phosphorus-
based process requiring additional preparation of the substrate.
(8) Synthetic transformations exploiting manganese metalation
of a C-Cl bond are scarce (manganese metalation of C-I and
C-Br bonds is easier than the analogous C-Cl bond).2 (9)
Finally, this methodology represents the first example of a
manganese-mediated sequential reaction.
In addition to these points, this sequential process can also
be utilized to stereoselectively obtain trisubstituted (E)-R,â-
unsaturated esters 5. The reaction was carried out under the same
reaction conditions utilizing, in this case, ethyl 2,2-dichloro-
This model assumes that the transformation of diastereoiso-
meric mixture 7 leads only to the stereoisomer of appropriate
conformation for coordination of the manganese center by the
alcoholate.
(22) The coupling constant between the olefinic protons of compounds
3 were in accordance with the average literature values: Silverstein, R.
M.; Bassler, G. C.; Morrill T. C. In Spectrometric Identification of Organic
Compounds; John Wiley and Sons: New York, 1991; Chapter 4, Appendix
F, p 221. In addition, values of coupling constants of olefinic protons were
in accordance with the values described in the literature for analogous
alkenes, see references 5b, 5c, 10a, 16, and 25.
(23) Aldrich Catalogue (2005-2006): 1 mmol CrCl2, 5.8 euro; 1 mmol
SmI2 (prepared by the method described in Concello´n, J. M.; Rodr´ıguez-
Solla, H.; Bardales, E.; Huerta, M. Eur. J. Org. Chem. 2003, 1775-1778),
1.1 euro; 1 mmol Mn* (prepared by the method described in reference 2d),
0.5 euro.
Conclusions
We have presented a general and very attractive synthesis of
R,â-unsaturated esters in high yields and with total E-stereo-
selectivity, in which the C-C double bond is di- or trisubsti-
tuted. This transformation, starting from readily available and
(24) Wittig reactions carried out with enolizable carbonyl compounds
can generate alkenes in very low yield: Maryanoff, B. E.; Reitz, A. B.
Chem. ReV. 1989, 89, 863-927.
(25) Concello´n, J. M.; Pe´rez-Andre´s, J. A.; Rodr´ıguez-Solla, H. Angew.
Chem., Int. Ed. 2000, 39, 2773-2775.
4398 J. Org. Chem., Vol. 72, No. 12, 2007

Synthesis of (E)-R,â-Unsaturated Esters
SCHEME 2. Proposed Mechanism of the Sequential Reaction
(5 mL) was added dropwise and stirred for 15 min. The mixture
was warmed to room temperature and then quenched with an
aqueous saturated solution of NH4Cl (20 mL) followed by extraction
with diethyl ether (3 × 20 mL). Usual workup provided crude
products 4a and 4b, which were purified by distillation.
cheap dichloroesters and a variety of aldehydes, takes place
through a sequential reaction: (a) an aldol-type reaction in the
first step, followed by (b) a â-elimination reaction in the second.
The reaction is promoted by the inexpensive Mn*, is the first
example of a sequential process, and is the second example of
a complete stereoselective â-elimination process, promoted by
manganese. The method described herein is more efficient than
our previously described methods mediated by SmI2 or CrCl2
and constitutes an advantageous choice for preparation of (E)-
R,â-unsaturated esters. A mechanism has been proposed to
explain this transformation. Studies directed toward the use of
active manganese to promote other sequential reactions are
currently under investigation within our laboratory.
Ethyl 2,2-Dichloropropionate (4a).27 Pale yellow oil (3.59 g,
75%, yield). 1H NMR (300 MHz, CDCl3): δ 4.31 (q, J ) 7.0 Hz,
2 H), 2.26 (s, 3 H), 1.33 (t, J ) 7.0 Hz, 3 H). 13C NMR (75 MHz,
CDCl3): δ 166.2 (C), 80.0 (C), 67.3 (CH2), 34.1 (CH3), 18.8 (CH3).
Ethyl 2,2-Dichloro-3-phenylpropionate (4b). Pale yellow oil
1
(4.29 g, 62% yield). H NMR (300 MHz, CDCl3): δ 7.38-7.35
(m, 5 H), 4.35 (q, J ) 7.0 Hz, 2 H), 3.78 (s, 2 H), 1.37 (t, J )
7.0 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ 165.6 (C), 133.2
(C), 131.1 (2 x CH), 128.0 (2 × CH), 127.8 (CH), 83.7 (C), 63.7
(CH2), 50.2 (CH2), 13.7 (CH3). MS (70 eV, EI) m/z (%) 246 [M+,
<1], 210 (51), 91 (100), 77 (37), 51 (34). IR (neat): 2989, 1763,
1454, 1259, 862 cm-1. Rf ) 0.62 (hexane/EtOAc 10/1). Anal. Calcd
for C11H12Cl2O2: C, 53.46; H, 4.89. Found: C, 53.83; H, 4.15.
General Procedure for the Synthesis of (E)-R,â-Unsaturated
Esters 3 and 5. The slurry of Mn* (2.5 mmol, 8.5 mL) in THF
was added to a stirred solution of ethyl 1,1-dichloroacetate
(0.6 mmol, 0.08 g) and the corresponding aldehyde (0.5 mmol) in
THF (2 mL) under a nitrogen atmosphere. The mixture was refluxed
for 3 h before it was quenched with HCl 3 M. The organic material
was extracted with diethyl ether (3 × 20 mL), the combined organic
extracts were washed sequentially with HCl 3 M (2 × 10 mL),
NaHCO3 (saturated, 2 × 20 mL), Na2S2O3 (saturated, 2 × 20 mL),
and brine (2 × 20 mL) and dried over Na2SO4. Solvents were
removed in vacuo. Purification by flash column chromatography
on silica gel (hexane/EtOAc 10/1) provided pure compound 3 or
5.
Experimental Section
Preparation of Highly Active Manganese (Mn*). A mixture
of lithium (26 mmol, 0.18 g) and 2-phenylpyridine (4 mmol, 0.98
mL) in THF (20 mL) under nitrogen atmosphere was stirred for 1
h. In a separate flask a solution of the complex Li2MnCl4 was
prepared by stirring a suspension of anhydrous MnCl2 (13 mmol,
1.62 g) and LiCl (26 mmol, 1.10 g) in THF (20 mL) for 30 min.
Then, this yellow solution was added at room temperature with a
syringe to the 2-phenylpyridine/lithium solution previously prepared
and was stirred under a nitrogen atmosphere at room temperature
for 1 h. The black slurry was allowed to stir at room temperature
for 3 h.
tert-Butyl Dichloroacetate (2c).26 A mixture of dichloroacetyl
chloride (20 mmol, 1.92 mL) and t-BuOH (40 mmol, 3.82 mL)
was refluxed in dry CH2Cl2 (55 mL) for 5 h. After that time, the
mixture was quenched with aqueous 1.0 M HCl (3 × 30 mL) and
extracted with dichloromethane. The combined extracts were dried
over Na2SO4 and the solvent was removed under vacuum to yield
Compounds 3a-g, 3i-m, 5a, and 5c displayed analytical data
in accordance with the published ones.5a-c,10a,16,25,28
Ethyl (E)-Trideca-2,12-dienoate (3h). Yellow oil (105 mg, 88%
yield). 1H NMR (300 MHz, CDCl3): δ 6.97 (dt, J ) 15.7, 6.8 Hz,
1 H), 5.81-5.75 (m, 2 H), 5.02-4.92 (m, 2 H), 4.19 (q, J )
7.2 Hz, 2 H), 2.23-2.18 (m, 2 H), 2.16-2.01 (m, 2 H), 1.46-1.27
(m, 15 H). 13C NMR (75 MHz, CDCl3): δ 166.6 (C), 149.3 (CH),
139.0 (C), 121.1 (CH), 114.0 (CH2), 59.9 (CH2), 33.7 (CH2), 32.0
(CH2), 29.2 (2 × CH2), 28.9 (2 × CH2), 28.7 (CH2), 27.9 (CH2),
14.2(CH3). MS (70 eV, EI) m/z (%) 238 [M+, <1], 150 (23), 81
(70), 55 (100), 41 (89). HRMS (70 eV) calcd for C15H26O2,
1
product 2c (3.63 g, 98% yield). H NMR (300 MHz, CDCl3): δ
5.71 (s, 1 H), 1.40 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ 163.3
(C), 84.9 (C), 65.2 (CH), 27.4 (3 × CH3).
Synthesis of Starting Materials 4a and 4b. A solution of
lithium diisopropylamide [prepared from n-BuLi (36 mmol,
14.4 mL, 2.5 M solution in hexane) and diisopropylamine (40 mmol,
5.8 mL) in THF (20 mL) at -78 °C] was added dropwise to a
stirred solution of the ethyl dichloroacetate (28 mmol, 4.4 g) in
dry THF (2 mL) at -78 °C, and the mixture was stirred for 15
min. After that time a solution of MeI or BnBr (28 mmol) in THF
(27) Tezuka, Y.; Hashimoto, A.; Ushizaka, K.; Imai, K. J. Org. Chem.
1990, 55, 329-333.
(28) Castelani, P.; Comasseto, J. V. Tetrahedron 2005, 61, 2319-2326.
(26) Parham, W. E.; Twelves, R. R. J. Org. Chem. 1957, 22, 730-734.
J. Org. Chem, Vol. 72, No. 12, 2007 4399

Concello´n et al.
238.1933; found, 238.1930. IR (neat): 2927, 1723, 1655, 1180,
980 cm-1. Rf ) 0.45 (hexane/EtOAc 10/1).
(m, 5 H), 7.06 (t, J ) 7.5 Hz, 1 H), 4.23 (q, J ) 7.2 Hz, 2 H), 3.78
(s, 2 H), 2.30-2.25 (m, 2 H), 1.87 (hp, J ) 6.6 Hz, 1 H), 1.31
(t, J ) 7.2 Hz, 3 H), 1.03 (d, J ) 6.6 Hz, 6 H). 13C NMR
(75 MHz, CDCl3): δ 167.7 (C), 142.9 (CH), 139.9 (C), 131.5 (C),
128.2 (4 × CH), 125.8 (CH), 60.4 (CH2), 37.9 (CH2), 32.3 (CH2),
28.3 (CH), 22.5 (2 × CH3), 14.1 (CH3). MS (70 eV, EI) m/z (%)
246 [M+, 73], 157 (36), 129 (100), 117 (47), 91 (70). HRMS
(70 eV) calcd for C16H22O2, 246.1620; found, 246.1627. IR (neat):
2958, 1711, 1453, 698 cm-1. Rf ) 0.52 (hexane/EtOAc 10/1).
Ethyl (E)-2-Benzyldec-2-enoate (5b). Pale orange oil (123 mg,
85% yield). 1H NMR (300 MHz, CDCl3): δ 7.18-7.08 (m, 5 H),
6.85 (t, J ) 7.5 Hz, 1 H), 4.05 (q, J ) 7.1 Hz, 2 H), 3.60 (s, 2 H),
1.18-1.11 (m, 15 H), 0.79 (t, J ) 6.9 Hz, 3 H). 13C NMR
(75 MHz, CDCl3): δ 167.7 (C), 144.0 (CH), 139.9 (C), 130.9 (C),
128.2 (4 × CH), 125.8 (CH), 60.4 (CH2), 32.3 (CH2), 31.7 (CH2),
29.3 (CH2), 29.0 (CH2), 28.9 (CH2), 28.6 (CH2), 22.5 (CH2), 14.1
(CH3), 13.9 (CH3). MS (70 eV, EI) m/z (%) 288 [M+, 60], 171
(25), 130 (100), 115 (38), 91 (81). HRMS (70 eV) calcd for
C19H28O2, 288.2089; found, 288.2085. IR (neat): 2927, 1712, 1454,
698 cm-1. Rf ) 0.45 (hexane/EtOAc 10/1).
Acknowledgment. We thank the Ministerio de Educacio´n
y Ciencia (CTQ2004-1191/BQU) for financial support. J.M.C.
thanks Carmen Ferna´ndez-Flo´rez for her time. H.R.S. and P.D.
thank the Ministerio de Educacio´n y Ciencia for a Ramo´n y
Cajal Contract (Fondo Social Europeo) and Principado de
Asturias for a predoctoral fellowship, respectively. Our thanks
to Euan C. Goddard for his revision of the English.
Ethyl (E)-2,5-Dimethylhex-2-enoate (5d). Yellow oil (58 mg,
1
68% yield). H NMR (300 MHz, CDCl3): δ 6.80 (t, J ) 7.5 Hz,
1 H), 4.21 (q, J ) 7.0 Hz, 2 H), 1.86-1.68 (m, 3 H), 1.84 (s, 3 H),
1.32 (t, J ) 7.0 Hz, 3 H), 0.94 (d, J ) 6.6 Hz, 6H). 13C NMR
(75 MHz, CDCl3): δ 168.3 (C), 141.2 (CH), 128.6 (C), 60.3 (CH2),
36.6 (CH2), 28.2 (CH), 22.4 (2 × CH3), 14.2 (CH3), 12.4 (CH3).
MS (70 eV, EI) m/z (%) 170 [M+, 33], 155 (25), 141 (52), 125
(100), 97 (81). IR (neat): 2961, 1728, 1265, 705 cm-1. Rf ) 0.46
(hexane/EtOAc 10/1). Anal. Calcd for C10H18O2: C, 70.55; H,
10.66. Found: C, 70.98; H, 10.23.
Supporting Information Available: Copies of 1H and 13C NMR
spectra for new compounds 3, 4, and 5. This material is available
free of charge via the Internet at http://pubs.acs.org.
Ethyl (E)-2-Benzyl-5-methylhex-2-enoate (5e). Colorless oil
1
(108 mg, 88% yield). H NMR (300 MHz, CDCl3): δ 7.37-7.25
JO070209W
4400 J. Org. Chem., Vol. 72, No. 12, 2007